In transdermal administration of a drug, stratum corneum works as a barrier to drug permeation, so the drug cannot sufficiently penetrate only by applying the drug on a skin surface. In contrast, perforation of corneum by using a minute needle, i.e. a microneedle can remarkably improve drug permeation efficiency compared to the application method. An article in which a large number of the microneedles are integrated on a substrate is a microneedle array. In addition, a product in which an adhesive tape for adhering the microneedle array to a skin and a cover sheet for maintaining an aseptic state until its use, etc. are added to the microneedle array in order to facilitate its use is called a microneedle patch. “Tape” as used herein means a film, or a fabric or a paper to which an adhesive agent is applied.
Manufacturing methods of the microneedles are greatly different whether a material of the microneedles is metal or resin, and various manufacturing methods have been currently tried and reported. Since the microneedles made of resin are easy to process and thus microneedles in various shapes can be made, much examination has been conducted. For example, a method in which a flat plate made of resin is molten with heating styli and stretch formed (Patent Document 1, 2); a method in which an aqueous solution of a water-soluble polymer is injected into a mold, and then dried and solidified to make the microneedles (Patent Document 3, 4); a manufacturing method in which polyglycolic acid in a molten state is compressed in a microneedle mold by pressing, and then solidified at low temperature (Patent Document 5), and a manufacturing method in which polyglycolic acid is injection-molded (Patent Document 6); etc. have been reported.
“Injection molding method” is a known method in which thermoplastic resin or the like is molten at high temperature and then high-pressure injected into a low temperature metal mold to solidify the resin. The resin used for injection-molding can include a general-purpose resin such as polyethylene resin, polypropylene resin, polyamide resin, and an engineering plastic such as polycarbonate resin, modified polyphenylene ether resin, polybutylene terephthalate resin, polyethylene terephthalate resin. Considering the worst case where the resin remains in a living body, as the thermoplastic resin suitable for the microneedle, a safety-guaranteed biodegradable resin such as polyglycolic acid resin, polylactic acid, and a copolymer thereof is preferable to a non-biodegradable resin such as polybutylene terephthalate resin.
When crystallinity is enhanced by adjusting an injection molding condition, strength of polyglycolic acid can be enhanced (Patent Document 7). In order to obtain polyglycolic acid with crystallinity of 5% or more, the resin should be injection-molded in a relatively high temperature condition where a resin temperature is 230-270° C. and a metal mold temperature is 80-130° C. (Patent Document 8). These polyglycolic acid molded articles are goods for consumer industrial application and relation between physical properties and crystallizability in the microneedle is not suggested, so it has been unexpected whether the physical properties of the microneedle are completely changed by crystallization in molding.
Furthermore, there is not currently a document in which correlation between the molding condition (especially the metal mold temperature) and the physical properties of the microneedle when the microneedles are manufactured by the injection molding method is examined based on experienced knowledge “Compressive strength per one needle should be 0.056 N or more to penetrate a skin” (Non-Patent Document 1). In particular, there is not a report in which a condition for manufacturing microneedles with a sharp tip by the injection molding method using polyglycolic acid, polylactic acid, and a copolymer thereof as the material is examined in detail.